FOXO1 Regulates Periodontal Inflammation Through Dendritic Cells

Objectives: The goal of the studies was to test the hypothesis that FOXO1 in dendritic cells plays an important role in activating the adaptive immune response.
Methods: FOXO1 lineage specific deleted CD11c.Cre⁺FOXO1^L/L and littermate control CD11c.Cre^-FOXO1^L/L mice (n=10) were inoculated with P. gingivalis compared to vehicle alone. Bacteria-specific antibody production was tested by ELISA. Dendritic cell to lymph node homing in vivo was determined by flow cytometry. Dendritic cell migration, adhesion to lymphocytes and phagocytosis of bacteria was tested in FOXO1 deleted dendritic cell compared to dendritic cell from matched control mice. Dendritic cells were transfected with CCR7 and ICAM-1 overexpression vectors compared to vector alone for rescue experiments. Statistical significance was determined by one-way ANOVA at the P < 0.05 level.
Results: There was 50-60% more periodontal bone loss in mice with DC specific FOXO1 deletion than WT mice after P. gingivalis inoculation (P<0.05). Anti-P. gingivalis IgG1 was reduced by 50% (p<0.05) in experimental vs control mice. The capacity of dendritic cells from CD11c.Cre⁺FOXO1^L/L mice to induce B lymphocytes to produce IgG was reduced by ~50% compared to dendritic cell from wildtype mice (P<0.05). FOXO1 deletion reduced 80% of dendritic cell homing to cervical lymph nodes (P<0.05). FOXO1 deletion significantly reduced dendritic cell migration (P<0.05). CCR7 over expression rescued the reduced migration by 66% (P<0.05). Deletion of FOXO1 significantly reduced dendritic cell binding to T cells (P<0.05) and phagocytosis of bacteria (P<0.05). ICAM-1 overexpression significantly rescued the effect of FOXO1 deletion on dendritic cell-T cell binding and bacterial phagocytosis (P<0.05).
Conclusions: FOXO1 in dendritic cells is needed to produce an adaptive immune response and protect against bacteria induced periodontal bone loss.